Copper-Catalyzed Oxidative C(sp3)?H/N?H Cross-Coupling of Hydrocarbons with P(O)?NH Compounds: the Accelerating Effect Induced by Carboxylic Acid Coproduct

Article abstract of DOI:10.1002/adsc.201801694

An chelation-assisted oxidative C(sp³)?H/N?H cross coupling of hydrocarbons with P(O)?NH compounds using copper acetate as catalyst is described. The results of kinetic experiments, mechanistic studies and DFT calculations demonstrate the importance of acetic acid coproduct as an additive for promoting the formation of intermediate bis((diphenylphosphoryl)(quinolin-8-yl)amino)copper (6), and consequently accelerating the construction of C(sp³)?N bond. The reaction proceeded efficiently with a wide array of hydrocarbons and P(O)?NH compounds, and the rate acceleration induced by the acetic acid coproduct have been repeatedly proven. Furthermore, the efficiency of small-scale reaction could be retained upon gram-scale synthesis in a continuous manner. (Figure presented.).

Full text of DOI:10.1002/adsc.201801694

Title: Copper-Catalyzed Oxidative C(sp3)−H/N−H Cross-Coupling of
Hydrocarbons with P(O)−NH Compounds: the Accelerating Effect
Induced by Carboxylic Acid Coproduct
Authors: Jian Lei, Yincai Yang, Lingteng Peng, Lesong Wu, Ping Peng,
Renhua Qiu, Yi Chen, Chak-Tong Au, and Shuang-Feng Yin
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801694
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper-Catalyzed Oxidative C(sp3)−H/N−H Cross-Coupling of
Hydrocarbons with P(O)−NH Compounds: the Accelerating
Effect Induced by Carboxylic Acid Coproduct
Jian Lei,a Yincai Yang,a Lingteng Peng,a Lesong Wu,a Ping Peng,a Renhua Qiu, a,* Yi
Chenb,*, Chak-Tong Au,c Shuang-Feng Yina,*
a
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering,
School of Materials Science and Engineering, Hunan University, Changsha 410082, People's Republic of China.
E-mail: renhuaqiu@hnu.edu.cn; sf_yin@hnu.edu.cn
School of Medicine, Hunan University of Chinese Medicine, Changsha 410208, People's Republic of China.
b
E-mail: cscy1975@163.com
c
College of Chemistry and Chemical Engineering, Hunan Institute of Engineering, Xiangtan 411104, Hunan, People's
Republic of China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. An chelation-assisted oxidative C(sp3)−H/N−H
well as a wide range of hydrocarbons (Scheme 1b).
cross coupling of hydrocarbons with P(O)−NH compounds For instance, White and Liu illustrated the
using copper acetate as catalyst is described. The results of
kinetic experiments, mechanistic studies and DFT
calculations demonstrate the importance of acetic acid
coproduct as an additive for promoting the formation of
preparation of linear amides from terminal alkenes
and N-tosylcarbamates using
a
Pd-catalyzed
protocol.[8] In the past decades, considerable
attentions have been paid to the development of
amidation methodologies through radical processes
intermediate
bis((diphenylphosphoryl)(quinolin-8-
yl)amino)copper (6), and consequently accelerating the
construction of C(sp3)−N bond. The reaction proceeded
efficiently with a wide array of hydrocarbons and P(O)−NH
compounds, and the rate acceleration induced by the acetic
acid coproduct have been repeatedly proven. Furthermore,
the efficiency of small-scale reaction could be retained
upon gram-scale synthesis in a continuous manner.
Keywords: copper-catalysis; cross dehydrogenative
coupling; hydrocarbons; P(O)−NH compounds; rate
acceleration
Progress in the transition metal-catalyzed C−N bonds
construction has advanced significantly,[1] and
efficient methods for preparing synthetically valuable
N-functionalized amides starting from ubiquitous
C(sp3)−H bonds are now available.[2] Conventional
approaches for C(sp3)−H amidation proceed through
metal-nitrene/imido
intermediates.[3−7]
bromamines-T,[5]
Various
functionalized compounds such as iminoiodinanes[3],
chloramine-T,[4]
N-
tosyloxycarbamates,[6] and organoazides[7], etc. can be
used as nitrogen sources for producing secondary
amides with the transfer of nitrene (Scheme 1a). In
contrast, the direct amidation of C(sp3)−H bonds via
oxidative C−H/N−H dehyrogenative coupling is more
attractive in terms of atom economy and tolerance
toward both primary and secondary amide reagents as
Scheme 1. Transition metal-catalyzed C(sp3)−H amidation.
1
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
by using catalyst systems based on earth abundant
first-row transition metals.[9−11] Among them, the
copper ones show perhaps the highest versatility in
these transformations.[10−11] In an early study, Katsuki
reported the first example .of copper-catalyzed allylic
and benzylic amidation based on a Kharasch-
Sosnovsky reaction by employing preformed
peroxycarbamates as oxidant as well as amine
component.[10] Following this pioneering work, a
number of copper-catalyzed radical amidation
reactions involving C(sp3)−H/N−H cross-coupling
have been exploited using peroxides as mild
oxidant.[11]
Table 1. Evaluation of reaction parameters.[a]
Recently, the development of chelation-assisted
transition-metal catalysis has provided
a new
complementary route for facile construction of
various C−N bonds.[12−13] Reactions of copper-
chelation system can be performed even at room
temperature.[13h,13j,13k]
The
intramolecular
dehydrogenative amidation protocol have been well
established by researchers such as Shi,[13a] Kanai,[13b]
Ge,[13c,13e] Shi,[13d] and Bedford[13g] (Scheme 1c). In
contrast, intermolecular processes are rarely reported.
[a]
Reaction conditions: phosphinamide 1a (0.3 mmol), Cu
catalysts, and oxidants dissolved in toluene 2a (1 mL)
under N2 atmosphere for 36 h.
There
are
two
cases
of
intermolecular
on this
[b]
31P NMR yield using triphenylphosphine oxide (0.3
dehydrogenative
amidation
based
mmol) as internal standard.
strategy,[13i−13j] in which only ether derivatives were
used as coupling partners and additional ligands were
required to promote the transformation (Scheme 1d).
Despite the limitations, we expect that this chelation-
assisted copper catalytic reaction can be an appealing
option for direct C(sp3)−H amidation.
[c] n.d. = not detected.
[d] Performed under air atmosphere.
[e] Performed under O2 atmosphere.
[f] Performed for 1h.
[g] SM = starting material.
Catalytic C−H functionalization involving metal-
chelation systems are catalytic cycles that are
potentially complex. For instance, Jutand and
coworkers illustrated an autocatalytic process in
pyridine-assisted ruthenium-catalyzed arylation of
functional arenes through utilizing the carboxylic
acid coproduct to promote the formation of
by taking advantage of the 8-aminoquinoline
auxiliary group,[13k] we applied our recently
developed CuII-catalyzed chelation system for
oxidative C(sp3)−H/N−H coupling, employing P,P-
diphenyl-N-(quinolin-8-yl)phosphinamide (1a) and
easily available toluene (2a) as model substrates. Our
initial investigation focused on C(sp3)−N formation
without the use of unnecessary additives (Table 1).
The use of a proper oxidant is critical for the reaction.
No reaction took place with tert-butyl hydroperoxide
(TBHP, entry 1) or benzoyl peroxide (BPO, entry 2).
If dicumyl peroxide (DCP) was used instead, 3a was
obtained in 54% yield (Table 1, entry 3). When di-
tert-butyl peroxide (DTBP) was used as oxidant, the
coupling reaction of 1a with toluene proceeded
efficiently to produce the coupling product 3a in 93%
yield, and a decrease in DTBP amount would
significantly lower the product yield (Table 1, entries
4 and 5). Increasing the loading of Cu(OAc)2 to 10
mol% and 20 mol% did not further elevate the yields
of 3a (Table 1, entries 6 and 7). If Cu(OAc)2 was
omitted, 3a was not formed (Table 1, entry 8).
Further studies showed that the use of alternative
copper salts or metal-based oxidants resulted in lower
yields of 3a (see supporting information for details).
Of significant relevance is the reaction atmosphere;
there was no reaction under air or oxygen (Table 1,
entries 9 and 10), indicating that oxygen has a
negative effect on reaction efficiency. It was
observed that reaction temperature has a direct
ruthenacycle
intermediate,
and
consequently
accelerating the C(sp2)−C(sp2) construction.[14] Such a
process is quite rare in copper catalysis.[15] A notable
exception is the recent success on copper-catalyzed
azide-alkyne cycloaddition reaction disclosed by
Whitesides et al.[15c] On the other hand, the
improvement by additional acetic acid was observed
in a few cases of C−N forming reactions.[9a,13g] The
strong development in these fields motivates us to
investigate the kinetics of the synthetic processes, and
to gain mechanistic insight into the C(sp3)−H
amidation that is based on the chelation-assisted
copper-catalysis protocol. Herein, we report a
aminoquinoline-assisted oxidative C(sp3)−H/N−H
cross-coupling using simple copper acetate as catalyst.
Additional ligand was not required in this
transformation. More to the point, a surprising rate
acceleration induced by the acetic acid coproduct was
found to take part in this reaction.
In view of the prevalence of phosphorus-
containing amides in catalytic, synthetic, and
biological molecules,[16] and our recent observation
that copper powder can facilely promote C−N cross-
coupling of phosphinamides and aryl boronic acids
2
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
influence on the time for complete reaction (Table 1,
entries 11–13). The reaction time could be
dramatically reduced from 36 h to 1 h when the
reaction took place at 140 °C, 150 °C or 160 °C,
albeit the instability of P–N bond in 1a resulted in
lower yields at the elevated temperatures (see
supporting information for details). Systematic tuning
of N-functionalized groups was carried out under the
optimal conditions, and yields of the corresponding
products are low to negligible (F1–F7). The results
indicate that an appropriate chelation is crucial in this
reaction.
To gain insight into this reaction, kinetic
experiments were performed. The generation of 3a
with time was monitored by 31P NMR spectroscopy
(Figure 1a). The time course of the model reaction
under optimal conditions exhibited a parabolic curve
in the initial 24 h, which suggests the reaction is
accelerated by a product formed in the reaction.[15]
After 24 h there is decrease of reaction rate plausibly
due to the exhaustion of starting material. Next, we
conducted the reaction in the presence of possible
products under standard conditions. There was no
t
detectable effect as a result of 3a or BuOH addition.
Because acetic acid could be formed in
intermolecular deprotonation of acetate ions
dissociated from Cu(OAc)2, its effect on the rate of
reaction was also evaluated. Delightfully, the reaction
time could be significantly reduced from 36 h to 23 h
with the addition of HOAc (10 mol%), and there was
the disappearance of the initiation period. Further
acceleration was not obvious when stoichiometric
amount (1 equiv) of acetic acid was added. Strong
decelerating effect of a base (Na2CO3) was observed
as a result of HOAc being neutralized. The reaction
kinetics was investigated within an initial period of
60 min, short enough to obtain data for accurate
evaluation of 3a generation rates at elevated
temperatures (Figure 1b). The time-course curves
obtained at 140 °C, 150 °C and 160 °C have
exponential appearance, and the accelerating effect at
160 °C is more obvious than that at 140 °C or 150 °C,
demonstrating that a controlled elevation of reaction
temperature could be beneficial for excelling the
accelerating effect.
Scheme 2. Mechanistic studies.
In the deuterium-labelling experiments of 1a, the
reaction using [D8]-toluene was slower than that
using toluene. Meanwhile, a demethylation reaction
of DTBP was found to take place in [D8]-toluene (not
detected in toluene).[11g,11j,17] In the 1H NMR spectrum
of products, when the reaction of 1a was performed
in a 1:1 mixture of toluene and [D8]-toluene, 1.80 H
was observed in the benzylic position, evidencing the
H-atom abstraction (HAA) of toluene is more
favorable than demethylation of DTBP and the C-D
scission of [D8]-toluene (Scheme 2a, kH/kD values up
to 9.0). The effect of radical scavengers was also
examined (Scheme 2b). The addition of TEMPO,
BHT or 1,4-benzoquinone resulted in complete
Figure 1. a) Time course of the model reaction at 100 °C
for 36 h. Relative intensity of desired product 3a with time:
no additive (■), in the presence of 1 equiv of 3a (◊), 2
t
equiv of BuOH (○), 10 mol% of HOAc (●), 1 equiv of
HOAc (♦) or 10 mol% of Na2CO3 (▲). b) Time-course of
model reaction at 140 °C (■), 150 °C (●) and 160 °C (▲)
for 1 h.
3
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
quenching of the reaction. With the successful
isolation of 2-benzylcyclohexa-2,5-diene-1,4-dione
(5), the involvement of benzyl radical in the reaction
is confirmed.
The trapping of CuII species 6 allowed a detailed
investigation into the mechanism (Scheme 2c).
Treatment of 1a with Cu(OAc)2 (50 mol%) under
nitrogen at 100 °C for 20 h produced an intermediate
bis((diphenylphosphoryl)(quinolin-8-
yl)amino)copper (6) in 90 % isolated yield (eq 1).
The structure of CuII species 6 attached with two
HOAc molecules (originated from 1a deprotonation),
was unambiguously characterized by X-ray
analysis.[18] The species 6 could be efficiently
obtained after 10 min at 160 °C, evidencing that the
elevation of temperature is beneficial for 1a
coordination with Cu(OAc)2 (eq 2). The starting
materials were recovered with the addition of Na2CO3
(10 mol%), revealing the retarding effect of a base
(eq 3). The reaction of CuII species 6•2HOAc with
toluene in the presence of DTBP (2 equiv) afforded
3a in 99% yield within 10 h (eq 4). The time course
of the stoichiometric reaction showing a linear grown
of 3a, indicating the CuII species 6 is not an off-cycle
“spectator” intermediate (Figure 2a).[15b] No reaction
took place with K2S2O8, which is able to abstract H-
Figure 3. Model reaction in the presence of additional acid
(10 mol% of tBuC(O)OH, PhC(O)OH, Ph2P(O)OH,
CF3C(O)OH, HCl, HBr or H2SO4) at 100 °C for 23 h.
Because the reaction is induced by acetic acid, the
influence of alternative acids was investigated
(Figure 3). Similar acceleration effects were
obviously observed through the addition of pivalic or
benzoic acid (10 mol%), giving the desired product in
91% and 90% yields within 23 h, respectively. With
such notation, it is envisioned that the scope of
copper carboxylate catalysts can be further enlarged.
The addition of diphenylphosphinic acid (10 mol%)
seriously limited the reaction efficiency, indicating
that phosphoric acid prejudices the current catalysis
system. In addition, the instability of P–N bond in
substrate 1a induced by the strong acidity also results
in poor reactivity, as in the reactions with the addition
t
atom in hydrocarbons without generating BuO•
radical (eq 5).[19] In view of the fact that Cu(OtBu)2
can be employed as a catalyst in this coupling
reaction (see supporting information for details), we
deduce that there are two potential functions of
t
DTBP in the transformation: (1) generating BuO•
radicals to engage in HAA of toluene; (2)
participating in the formation of copper alkoxide
intermediate.
of
trifluoroacetic
acid,
hydrochloric
acid,
hydrobromic acid or sulfuric acid.
On the basis of above results and previous
reports,[11d−g,13i−j] a plausible mechanism is proposed
as illustrated in Scheme 3. After complexation of
substrate 1a with Cu(OAc)2, CuII species A is formed.
Then intermolecular deprotonation of N–H bond in
another 1a by the ligated acetate in species A takes
place, leading to CuII species 6. The acetic acid
coproduct promotes the formation of species 6,
consequently accelerates the overall reaction. DFT
calculations clarify the role of HOAc as an additive
for promoting the complexation of species A with 1a;
the energy barrier via transition state TS2 (18.4
kcal/mol) is much lower than that via TS1 (29.4
kcal/mol) (Figure 4). This is in good agreement with
the experimental fact that the presence of carboxylic
acid is essential to accelerate the reaction. The
benzylic radical generated via HAA from toluene by
tBuO• radical derived from DTBP decomposition can
be rapidly captured by species 6 to afford product 3a,
together with the generation of CuI species B, which
could undergo a kind of Kharasch-Sosnovsky
Figure 2. Time course of the stoichiometric reaction of
CuII species 6·2HOAc with toluene at 100 °C for 10 h.
Yields were calculated on the basis of one ligand bound to
6•2HOAc.
4
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
methylthiophene,
and
2-methylquinoline.
Unfortunately, no corresponding products could be
found.
Table 2. Substrate scope of hydrocarbons.[a]
Scheme 3. Proposed mechanism.
reaction with DTBP to afford CuII alkoxide C. Facile
acid/base chemistry between 1a and species D
regenerates species 6, and the accumulation of acetic
acid further accelerates the reaction. With the
exhaustion of 1a, anion exchange between species D
and HOAc takes place. Subsequently, the benzylic
radical may react directly with the CuII center or
phosphinamide ligand in species A to form the
intermediate D1[11g,13i−j] or D2[11d−g]
.
Reductive
elimination of species D affords the product 3a along
with CuI species which would be re-oxidized to CuII
catalyst with DTBP as a terminal oxidant.
Figure 4. Geometric structures of key transition states.
Having extensively investigated the mechanism,
we explored other kinds of substrates in this C(sp3)–
N formation reaction (Tables 2 and 3). A wide variety
of functional groups on the toluene derivatives, even
bromide and iodide, are tolerated in this catalytic
system (3b–3q). Showing high compatibility for this
reaction, the hydrocarbons with 3° benzylic C–H
bond give the corresponding product 3r with good
site selectivity. Notably, tert-butylbenzene and
hexane without benzylic C–H bond can be also
activated at the terminal C(sp3)–H bond to give
respectable yields of 3s and 3t, respectively. The
presence of primary benzylic C–H resulted in almost
exclusive products (3u–3x) in good yields,
evidencing the high reactivity of primary benzylic C–
H bond. We also examined the reactions using
electron-deficient arenes and heteroarenes, e.g. 1-
methyl-2-nitrobenzene, 1-methyl-3-nitrobenzene, 1-
[a] Conditions A: 1a (0.3 mmol), 2b–2x (1 mL), Cu(OAc)2
(0.015 mmol), DTBP (0.6 mmol), N2, 100 °C, 36 h.
Conditions B: 1a (0.3 mmol), 2b–2x (1 mL), Cu(OAc)2
(0.015 mmol), DTBP (0.6 mmol), N2, 100 °C, 23 h.
Conditions C: 1a (0.3 mmol), 2b–2x (1 mL), Cu(OAc)2
(0.015 mmol), DTBP (0.6 mmol), HOAc (0.03 mmol), N2,
100 °C, 23 h. The reaction conditions, A–C, used are
indicated within parentheses. Yield was determined by 31P
methyl-4-nitrobenzene,
2-methylpyridine,
2-
5
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
NMR analysis, using triphenylphosphine oxide (0.3 mmol)
as internal standard. Q = 8-quinolyl group.
[b] Isolated yields.
Finally, to highlight the synthetic utility of the
present protocol, 3a was synthesized in gram scale as
well as in a continuous manner (Scheme 4). The
efficiency of the small-scale reaction was retained,
delivering 3a in 84% isolated yield (eq 6). In
consideration that the rate of reaction could decrease
due to the decay of starting material, we explored
whether reactivity could be also retained at the
efficient state by continuous feeding of starting
[c] n.i. = not isolated
Table 3. Substrate scope of P(O)−NH compounds.[a]
Scheme 4. Gram scale and continuous synthesis.
material. To our delight, after 23 h treatment of 1a
with Cu(OAc)2 (5 mol%), the accelerating stage
could be retained when the reaction was fed dropwise
with a mixture of starting material, oxidant and
coupling partner, and 3a could be obtained in 90%
isolated yield under nitrogen at 100 °C for 18 h (eq 7).
Note that the continuous feeding was performed
without refreshment or new addition of copper
catalyst. The results point to
a
potential
[a]
Conditions A: 1b–1j (0.3 mmol), 2a (1 mL), Cu(OAc)2
industrialization window for producing tertiary
unsymmetrical phosphorus-containing amides.
(0.015 mmol), DTBP (0.6 mmol), N2, 100 °C, 36 h.
Conditions B: 1b–1j (0.3 mmol), 2a (1 mL), Cu(OAc)2
(0.015 mmol), DTBP (0.6 mmol), N2, 100 °C, 23 h.
Conditions C: 1b–1j (0.3 mmol), 2a (1 mL), Cu(OAc)2
(0.015 mmol), DTBP (0.6 mmol), HOAc (0.03 mmol), N2,
100 °C, 23 h. The reaction conditions, A–C, used are
indicated within parentheses. Yield was determined by 31P
NMR analysis, using triphenylphosphine oxide (0.3 mmol)
as internal standard. Q = 8-quinolyl group.
In conclusion, we have developed a copper-
catalyzed C(sp3)−N cross-coupling reaction based on
aminoquinoline-assisted oxidative C(sp3)−H/N−H
cross-coupling of hydrocarbons with P(O)−NH
compounds. The results of kinetic experiments,
mechanistic studies, DFT calculations and rate
acceleration of a wide substrate scope repeatedly
demonstrate the accelerating effect induced by the
acetic acid coproduct. It is a new strategy for the
construction of C(sp3)−N bonds via oxidative cross
dehydrogenative coupling. The key intermediate in
[b] Isolated yields.
The reaction also works well for an array of
diarylphosphinamides with either electron rich or
electron deficient group (7–12). Moreover,
dialkylphosphinamides and phosphoramide were
found compatible in this reaction (13, 14 and 15). The
generality of the accelerating effect was further
verified by examining the 31P NMR yield of
corresponding product obtained within 23 h, and that
with the addition of acetic acid (10 mol%), separately
(Condition B–C). The reaction rate could be
somewhat accelerated by catalytic amount of acetic
acid (3b–15). The results demonstrate that the
electronic and steric properties of hydrocarbons and
P(O)−NH compounds can affect both the efficiency
of the coupling reaction and the accelerating effect
induced by acetic acid. The structure of 3a was
characterized by X-ray crystallography,[18] and those
of the other products were assigned by analogy.
this
transformation,
bis((diphenylphosphoryl)(quinolin-8-
yl)amino)copper, (6) was isolated and characterized
by X-ray analysis. The accelerating effect is further
exemplified by gram-scale synthesis of product 3a in
a continuous manner, with the efficiency of small-
scale reaction being retained. Further investigations
on the reaction mechanism and bioactive application
of
the
synthesized
tertiary
amides
unsymmetrical
phosphorus-containing
are
currently
underway in our laboratory.
Experimental Section
General
Procedure
for
Copper-Catalyzed
C(sp3)−H/N−H Cross Coupling of Hydrocarbons with
6
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10.1002/adsc.201801694
Advanced Synthesis & Catalysis
P(O)−NH Compounds and Determination of
[4] a) D. P. Albone, S. Challenger, A. M. Derrick, S. M.
Fillery, J. L. Irwin, C. M. Parsons, H. Takada, P. C.
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11784−11791; c) R. Bhuyan, K. M. Nicholas, Org. Lett.
2007, 9, 3957−3959.
Accelerating Effect.
An oven-dried 25 mL Schlenk tube was charged with
phosphorus-containing amide (0.3 mmol), Cu(OAc)2 (2.7
mg, 5 mol%), DTBP (114 µL, 2 equiv) and hydrocarbons
(1 mL) under nitrogen atmosphere with stirring at 100 °C
for 36 h. The mixture was then cooled to room temperature,
diluted with CH2Cl2 (2 mL), and filtered through a celite
pad. The yield of product was determined by 31P NMR
spectra of the filtrate, using triphenylphosphine oxide (83.4
mg, 0.3 mmol) as internal standard. After the concentration
of the filtrate in vacuo, the residues were purified by silica
gel flash chromatography column to give the
corresponding product. The generality of accelerating
effect by acetic acid coproduct was further verified by
examining the 31P NMR yield of the corresponding product
obtained within 23 h, and that with the addition of acetic
acid (10 mol%), separately.
[5] a) J. D. Harden, J. V. Ruppel, G.-Y. Gao, X. P. Zhang,
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[6] a) H. Lebel, K. Huard, S. Lectard, J. Am. Chem. Soc.
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Chem.-Eur. J. 2008, 14, 6222–6230.
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Acknowledgements
The authors thank the National Natural Science Foundation of
China (Nos. 21571060, 21676076, 21725602) for financial
support. R. Qiu thanks Prof. Nobuaki Kambe, Prof. Takanori
Iwasaki (Osaka University) and Prof. Yuanzhi Xia (Wenzhou
University) for helpful discussion. C.T. Au thanks Hunan
University for an adjunct professorship.
[8] a) S. A. Reed, M. C. White, J. Am. Chem. Soc. 2008,
130, 3316−3318; b) G. Liu, G. Yin, L. Wu, Angew.
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8
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UPDATE
Copper-Catalyzed Oxidative C(sp3)−H/N−H Cross-
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